Activin

Protein
Name=inhibin, beta A (activin A, activin AB alpha polypeptide)

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caption=The Activin dimer, from 2ARV.pdb
Symbol=INHBA
AltSymbols=
HGNCid=6066
Chromosome=7
Arm=p
Band=
LocusSupplementaryData=15-p13
ECnumber=
OMIM=147290
EntrezGene=3624
RefSeq=NM_002192
UniProt=P08476
PDB=Protein
Name=inhibin, beta B (activin B, activin AB beta polypeptide)


caption=
Symbol=INHBB
AltSymbols=
HGNCid=6067
Chromosome=2
Arm=
Band=
LocusSupplementaryData=cen-q13
ECnumber=
OMIM=147390
EntrezGene=3625
RefSeq=NM_002193
UniProt=P09529
PDB=

Activin is a peptide that enhances FSH synthesis and secretion and participates in the regulation of the menstrual cycle. It does the opposite as inhibin. Many other functions have been found to be exerted by activin, including their roles in cell proliferation, differentiation, apoptosis [Chen YG, Wang Q, Lin SL, Chang CD, Chung J, and Ying SY. Activin Signaling and its Role in Regulation of Cell Proliferation, Apoptosis and Carcinogenesis. Exp Biol Med. 2006; 231: 534-544. ] , metabolism, homeostasis, immune response, wound repair [Sulyok S, 20 M, Alzheimer C, Werner S. Activin: an important regulator of wound repair, fibrosis, and neuroprotection. Molecular and Cellular Endocrinology. 2005; 225: 126-132.] , and endocrine function

Like inhibin (and AMH) activin belongs to TGF-β superfamily.

tructure

Activins are formed by the homo- or heterodimerization of activin beta subunits. In mammals, four subunits have been described called activin beta A, activin beta B, activin beta C and activin beta E. Activin beta A and beta B are identical to the two beta subunits of inhibin. A fifth subunits, activin beta D has been discribed in Xenopus laevis. Two activin beta A subunits give rise to activin A, one beta A and one beta B subunit gives rise to activin AB and so on. Various, but not all theoretically possible, heterodimers have been described. [Xu P, Hall AK. The role of activin in neuropeptide induction and pain sensation. Dev Biol. 2006 Nov 15;299(2):303-9 http://www.ncbi.nlm.nih.gov/pubmed/16973148] , [Deli A, Kreidl E et al. "Activins and activin antagonists in hepatocellular carcinoma." World J Gastroenterol. 2008 Mar 21;14(11):1699-709. PMID 18350601]

The subunits are linked by a single covalent disulfide bond.

Function

Activin is produced in the gonads, pituitary gland, placenta and other organs:

* In the ovarian follicle, activin increases FSH binding and FSH induced aromatization. It participates in androgen synthesis enhancing dn|LH action in the ovary and testis. In the male, activin enhances spermatogenesis.

* Activin is strongly expressed in wounded skin, and overexpression of activin in epidermis of transgenic mice improves wound healing and enhances scar formation. Its action in wound repair and skin morphogenesis is through stimulation of keratinocytes and stromal cells in a dose-dependent manner. [Bamberger C, Schärer A, Antsiferova M, Tychsen B, Pankow S, Müller M, Rülicke T, Paus R, and Werner S. Activin Controls Skin Morphogenesis and Wound Repair Predominantly via Stromal Cells and in a Concentration-Dependent Manner via Keratinocytes. American Journal of Pathology. 2005; 167 (3): 733-741. ]

* Activin also regulates the morphogenesis of branching organs such as the prostate, lung, and especially kidney. Activin A increased the expression level of type I collagen suggesting that activtin A acts as a potent activator of fibroblasts.

Mechanism

As with other members of the superfamily, activins interact with two types of cell surface transmembrane receptors (Types I and II) which have intrinsic serine/threonine kinase activities in their cytoplasmic domains.

Activin binds to the Type II receptor and initiates a cascade reaction that leads to the recruitment, phosphorylation, and activation of Type I activin receptor. This then interacts with and then phosphorylates Smad2 and Smad3, two of the cytoplasmic Smad proteins.

Smad3 then translocates to the nucleus and interacts with Smad4 through multimerization, resulting in their modulation as transcription factor complexes responsible for the expression of a large variety of genes.

References

External links

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